Long-term TNF inhibitor use in rheumatoid arthritis not linked to increased cancer risk
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There is no increased risk for cancer overall associated with the long-term use of TNF inhibitors for rheumatoid arthritis, according to data published in Rheumatology.
“Studies on cancer risks with TNF inhibitors have been based on relatively short follow-up (few studies with a medium follow-up of more than 3 years), thus leaving questions on longer-term risks essentially unanswered,” Viking Huss, MD, of the Karolinska Institute and Karolinska University Hospital, in Stockholm, Sweden, and colleagues wrote. “This is concerning, as from a cancer induction and surveillance point of view, relevant time-frames may be much longer.”
“For non-TNFi biologic DMARDs, available safety data are based on data from clinical trial programs and (few) observational cohorts, with even shorter follow-up times than those available for TNFi,” they added. “So far, the output from these studies have been both reassuring and pointed to signals of potential risk increases. For targeted synthetic DMARDs, because of their later introduction, data on cancer risks from their use in clinical practice are scarce.”
To analyze the occurrence and relative risks for first-ever, non-cutaneous cancer — both overall and in 16 specific sites — in patients with RA receiving biologic and targeted synthetic disease-modifying antirheumatic drugs, Huss and colleagues conducted an observational, nationwide population-based cohort study. The primary data source was the Swedish Rheumatology Quality Register (SRQ), with additional information acquired through linkage with other national registers, including the National patient register (NPR), Prescribed drug register (PDR), Total population register, and Cancer register.
The researchers included data from 69,308 patients with RA treated with TNF inhibitors — adalimumab (Humira, AbbVie), certolizumab (Cimzia, UCB), etanercept (Enbrel, Amgen), golimumab (Simponi, Janssen) or infliximab (Remicade; Janssen, Johnson & Johnson) — or other biologic and targeted synthetic DMARDs — abatacept (Orencia, Bristol Myers Squibb), rituximab (Rituxan; Genentech, Biogen), baricitinib (Olumiant, Eli Lilly & Co.), tofacitinib (Xeljanz, Pfizer) and tocilizumab (Actemra, Genentech).
These data were then compared to those from patients with RA not treated with biologic and targeted synthetic DMARDs and matched to 109,532 individuals from the general population. The researchers used Cox regression to estimate incidence rates and hazard ratios, adjusting for co-morbidities and other health characteristics.
According to the researchers, there were 8,633 cases of incident cancer reported among patients with RA. The overall relative risk for cancer in those who received TNF inhibitors (HR = 1) was not increased, nor did it change over time since the start of treatment — nor over time on active treatment, nor based on attained age — compared with patients not treated with biologic and targeted synthetic DMARDs. In addition, there were no consistent signals for increased overall cancer risk for the other biologic and targeted synthetic DMARDs, with hazard ratios ranging from 1 to 1.2.
However, there were statistically significant estimates above 1 for abatacept, at 2 to 5 years of active treatment for older age groups, and between several of the biologic DMARDs and urinary tract cancer.
“In this large observational study with the, to our knowledge, hitherto longest average follow-up of cancer risks in patients with RA treated with b/tsDMARD in clinical practice, we did not observe any increase in the overall occurrence of cancer with TNFi, nor any trends with time since treatment start, time on active treatment, or attained age, compared with b/tsDMARD-naïve patients,” Huss and colleagues wrote. “For other bDMARDs, we noted no consistent signal of any increased overall cancer risks, even if certain relative risk estimates were (statistically significantly) above 1.”
“With respect to relative risks for the 16 specific cancer sites, we noted several statistically significant associations for urinary tract cancer with TNFi, rituximab as well as abatacept,” they added. “From a scientific point of view our results extends the safety profile of bDMARDs in RA, but also contain signals that call for replication in further studies, although at this stage, neither the consistency nor the magnitude of these signals currently seems to warrant changes to clinical practice.”
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